Gosal D, Ross O A, Toft M
Department of Neurology, Mater Misericordiae University Hospital, Dublin, Ireland.
Eur J Neurol. 2006 Jun;13(6):616-27. doi: 10.1111/j.1468-1331.2006.01336.x.
Since the first description of Parkinson's disease (PD) in 1817 attempts have been made to resolve the etiology of this common neurodegenerative disorder. In the last century the influence of heredity in PD was controversial. The identification of mutations in six genes responsible for Mendelian forms of PD; alpha-synuclein (SNCA), parkin (PRKN), ubiquitin C-terminal hydrolase L1 (UCH-L1), oncogene DJ-1, PTEN-induced putative kinase 1 (PINK1), and most recently leucine-rich repeat kinase 2 (LRRK2), has confirmed the role of genetics in familial forms of the disease. The exact relationship of these familial disorders and related genes to the more common sporadic form is currently uncertain. The identification of LRRK2 mutations and the association of common variants in SNCA and UCH-L1 in apparently sporadic late-onset disease indicate these genes may be of greater importance than previously believed. The protein products of the six genes are involved in different pathways of neurodegeneration and have opened new avenues of research. This focused research will lead to the development of novel targeted therapies, which may revolutionize the treatment of PD for a substantial proportion of patients.
自1817年首次描述帕金森病（PD）以来，人们一直试图解开这种常见神经退行性疾病的病因。在上个世纪，遗传因素在帕金森病中的作用存在争议。六个导致孟德尔形式帕金森病的基因突变的鉴定；α-突触核蛋白（SNCA）、帕金蛋白（PRKN）、泛素C末端水解酶L1（UCH-L1）、癌基因DJ-1、PTEN诱导的假定激酶1（PINK1），以及最近的富含亮氨酸重复激酶2（LRRK2），证实了遗传学在该疾病家族形式中的作用。目前尚不确定这些家族性疾病及相关基因与更常见的散发性形式的确切关系。LRRK2突变的鉴定以及明显散发性晚发型疾病中SNCA和UCH-L1常见变异的关联表明，这些基因可能比之前认为的更为重要。这六个基因的蛋白质产物参与了神经退行性变的不同途径，并开辟了新的研究途径。这种有针对性的研究将导致新型靶向治疗方法的开发，这可能会彻底改变相当一部分帕金森病患者的治疗方式。
